Brief report: Circulating markers of fibrosis are associated with immune reconstitution status in HIV-infected men.

INTRODUCTION: Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants. METHODS: HIV-infected men on ART for >1 year with cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n = 25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n = 49). HA and CXCL4 concentrations were measured via ELISA. RESULTS: Median pre-ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls. Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for controls. HIV infection duration was 23 years, with median time on ART 13 years for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations did not vary by eventual immune reconstitution status. Post-ART HA concentrations tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired pre-/post-ART samples, non-responders had greater HA increases and CXCL4 decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405 ng/mL, p = 0.01). CONCLUSIONS: Higher circulating concentrations of HA and lower concentrations of CXCL4 are associated with failure of immune reconstitution on ART.

Risk of lymphoma subtypes after solid organ transplantation in the United States.

BACKGROUND: Solid organ transplant recipients have high risk of lymphomas, including non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). A gap in our understanding of post-transplant lymphomas involves the spectrum and associated risks of their many histologic subtypes. METHODS: We linked nationwide data on solid organ transplants from the US Scientific Registry of Transplant Recipients (1987-2008) to 14 state and regional cancer registries, yielding 791 281 person-years of follow-up for 19 distinct NHL subtypes and HL. We calculated standardised incidence ratios (SIRs) and used Poisson regression to compare SIRs by recipient age, transplanted organ, and time since transplantation. RESULTS: The risk varied widely across subtypes, with strong elevations (SIRs 10-100) for hepatosplenic T-cell lymphoma, Burkitt's lymphoma, NK/T-cell lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma (both systemic and primary cutaneous forms). Moderate elevations (SIRs 2-4) were observed for HL and lymphoplasmacytic, peripheral T-cell, and marginal zone lymphomas, but SIRs for indolent lymphoma subtypes were not elevated. Generally, SIRs were highest for younger recipients (<20 years) and those receiving organs other than kidneys. CONCLUSION: Transplant recipients experience markedly elevated risk of a distinct spectrum of lymphoma subtypes. These findings support the aetiologic relevance of immunosuppression for certain subtypes and underscore the importance of detailed haematopathologic workup for transplant recipients with suspected lymphoma.

The multicenter AIDS Cohort Study, 1983 to .

The Multicenter AIDS Cohort (MACS), initiated in 1983 at the Johns Hopkins School of Public Health, the University of Pittsburgh School of Public Health, Northwestern University School of Medicine, and the UCLA School of Public Health, continues to conduct studies and publish key papers on the natural history of untreated and treated HIV infection in 6972 men-who-have-sex-with-men. Through May 2011, 1,490,995 specimens have been collected, 86,883 person-years of data accrued and 1195 scientific papers published in international journals.

Enhanced cytotoxicity of an anti-transferrin receptor IgG3-avidin fusion protein in combination with gambogic acid against human malignant hematopoietic cells: functional relevance of iron, the receptor, and reactive oxygen species.

The human transferrin receptor (hTfR) is a target for cancer immunotherapy due to its overexpression on the surface of cancer cells. We previously developed an antibody-avidin fusion protein that targets hTfR (anti-hTfR IgG3-Av) and exhibits intrinsic cytotoxicity against certain malignant cells. Gambogic acid (GA), a drug that also binds hTfR, induces cytotoxicity in several malignant cell lines. We now report that anti-hTfR IgG3-Av and GA induce cytotoxicity in a new broader panel of hematopoietic malignant cell lines. Our results show that the effect of anti-hTfR IgG3-Av is iron-dependent whereas that of GA is iron-independent in all cells tested. In addition, we observed that GA exerts a TfR-independent cytotoxicity. We also found that GA increases the generation of reactive oxygen species that may play a role in the cytotoxicity induced by this drug. Additive cytotoxicity was observed by simultaneous combination treatment with these drugs and synergy by using anti-hTfR IgG3-Av as a chemosensitizing agent. In addition, we found a concentration of GA that is toxic to malignant hematopoietic cells but not to human hematopoietic progenitor cells. Our results suggest that these two compounds may be effective, alone or in combination, for the treatment of human hematopoietic malignancies.

The effect of atopy, childhood crowding, and other immune-related factors on non-Hodgkin lymphoma risk.

OBJECTIVE: Since adult immune responsiveness is influenced by early childhood exposures, we examined the role of family size, history of atopic disease, and other childhood immune-related exposures in a multi-center case-control study of NHL. METHODS: Interviews were completed with 1,321 cases ascertained from population-based cancer registries in Seattle, Detroit, Los Angeles and Iowa, and with 1,057 frequency-matched controls, selected by random-digit dialing and from the Medicare files database. Multivariable logistic regression was used to estimate risk. RESULTS: A history of any allergy (excluding drug allergies), decreased risk of all NHL (Odds Ratio [OR] = 0.7, 95% Confidence Interval [CI] = 0.6-1.0), diffuse large B-cell lymphoma [DLBCL] (OR = 0.6, 95% CI = 0.4-0.9), and follicular NHL (OR = 0.7, 95 CI = 0.5, 1.0). A similar effect was observed for hay fever. A history of eczema was associated with an increased risk of follicular lymphoma (OR = 1.9, 95% CI = 1.1-3.4), but not DLBCL (OR = 1.1, 95% CI = 0.6-2.0). Asthma did not affect risk. Youngest compared to oldest siblings had a 90% increased risk of DLBCL (95% CI = 1.2-3.1; p for trend with increasing birth order = 0.006), but not follicular lymphoma (OR = 1.1, 95% CI = 0.6-1.8). CONCLUSIONS: We infer that some childhood and immune-related factors may alter NHL risk.

In situ detection of SOCS and cytokine expression in the uterine cervix from HIV/HPV coinfected women.

The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) and cytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-alpha and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-alpha was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-alpha, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-alpha and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.

Viral interleukin 6 stimulates human peripheral blood B cells that are unresponsive to human interleukin 6.

Cellular responsiveness to human interleukin 6 (hIL6) requires the expression of two receptor molecules: IL6-specific receptor (CD126'IL6R') and a nonspecific signal-transducing molecule (CD130'gp130'). Regulation of responsiveness to hIL6 is generally controlled by CD126'IL6R' expression. A viral homologue of hIL6 (vIL6) is encoded by human herpesvirus-8 and has biologic activity similar to hIL6 on a number of cell lines. vIL6 differs from hIL6 in its receptor utilization, requiring only CD130'gp130'. Total human B cells isolated from peripheral blood, which are predominantly CD126'IL6R'-negative, as well as sorted CD126'IL6R'-negative B cells, could be stimulated by recombinant vIL6, but not by hIL6, as indicated by induction of IL6-like signaling (STAT3 phosphorylation). This suggests that the ability of vIL6 to stimulate B cells expressing little or no CD126'IL6R' allows it to act on a larger pool of target B cells, compared to human IL6.

Effects of human papillomavirus-associated cells on human immunodeficiency virus gene expression.

OBJECTIVE: To examine the effects of soluble factors secreted by human papillomavirus (HPV)-associated cells on human immunodeficiency virus (HIV) expression. METHODS: Supernatants collected from cultured cervical biopsies and cervical cancer cell lines, and HPV-immortalized and normal keratinocytes were tested for the ability to induce HIV p24 production in two cell lines that contained latent HIV (the U1 monocytic line and the ACH-2 T cell line). Levels of HIV p24 were measured by enzyme-linked immunosorbent assay (ELISA). Culture supernatants were also assayed for the inflammatory cytokines interleukin 6, tumor necrosis factor, and interleukin 1 beta by ELISA. RESULTS: Supernatants from all epithelial cells tested upregulated HIV p24 expression in the U1 line but not in the ACH-2 cells. Only differentiated normal keratinocytes induced p24 production by ACH-2 cells. Neutralization of the cytokines, particularly interleukin 6, partially reduced the level of HIV-inducing activity in the culture supernatants. Additionally, cervical biopsies from HIV-infected women cultured in vitro also were able to induce HIV in U1 cells but not ACH-2 cells. CONCLUSIONS: Our results suggest that HPV infection of the cervix might influence HIV pathogenesis by inducing the production of immune and inflammatory factors that enhance HIV expression.

Peritoneal fluid interleukin-6 in women with chronic pelvic pain.

OBJECTIVE: To determine the relationship between peritoneal fluid concentrations of interleukin-6 (IL-6) and chronic pelvic pain symptomatology in women with adhesions, endometriosis, or no obvious intraperitoneal pathology. DESIGN: Clinical research study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Reproductive-aged women undergoing laparoscopy for the diagnosis of pelvic pain, infertility, or sterilization were selected. INTERVENTION(S): Peritoneal fluid was collected at the time of the laparoscopy and later assayed for IL-6. Subjects completed a pelvic pain questionnaire, and operative reports were used to obtain the underlying diagnosis. MAIN OUTCOME MEASURE(S): Interleukin-6 concentrations. RESULT(S): No correlation between the presence or absence of pelvic pain, findings of adhesions or endometriosis, and the concentration of peritoneal fluid IL-6 was observed. CONCLUSION(S): The cytokine IL-6 does not seem to play a role in the genesis of chronic pelvic pain in women with adhesions or endometriosis.

Serum sCD23 level in patients with AIDS-related non-Hodgkin's lymphoma is associated with absence of Epstein-Barr virus in tumor tissue.

The cytokine soluble CD23 (sCD23) acts as a B cell growth factor and is associated with Epstein-Barr virus (EBV) infection. To elucidate the role sCD23 might play in the pathogenesis of AIDS-related non-Hodgkin's lymphoma (AIDS NHL), 101 AIDS NHL patients from the Multicenter AIDS Cohort Study were studied. Serum sCD23 within 18 months prior to lymphoma diagnosis was measured for all patients and EBV in tumor tissue was ascertained for 49 patients. Tumor morphology and primary site were verified from pathology reports and tumor specimens. Bivariate tests and multivariate regression were employed to determine whether serum sCD23 correlated with tumor EBV, morphology, and primary site. Higher levels of serum sCD23 were associated with the absence of tumor EBV and with small noncleaved cell morphology. Thus, the serum sCD23 level does not appear to be mediated by EBV in these patients, but could be related to a pathogenetic mechanism of small noncleaved cell lymphoma.

Serum soluble CD23 level correlates with subsequent development of AIDS-related non-Hodgkin's lymphoma.

The cytokine soluble CD23 (sCD23) has been shown to act as a B cell growth factor and to be elevated in serum prior to development of AIDS-related non-Hodgkin's lymphoma (AIDS NHL). To further characterize the elevation of serum sCD23 in AIDS NHL patients and investigate its potential as a diagnostic test, a matched case-control study of AIDS NHL (n = 101) was nested within the Multicenter AIDS Cohort Study. Serum sCD23 was measured in cases' and controls' serum specimens at three different time periods (0-6, 6-12, and 12-18 months) and CD4+ thresholds (0-99, 100-199, and 200-299 cells/microl) prior to the case's NHL diagnosis. Changes in serum sCD23 over time were examined in AIDS NHL cases relative to controls, and t tests were performed to determine whether cases' serum sCD23 exceeded that of controls at each time period and CD4+ threshold. Overall, cases' median serum sCD23 levels were approximately double those of controls. Serum sCD23 concentration was positively correlated with lymphocyte counts for both cases and controls. The difference in cases' and controls' serum sCD23 levels became greater as AIDS NHL diagnosis date approached: in the 18 months preceding the case's NHL diagnosis, serum sCD23 was stable in cases but dropped in controls. Although this difference was statistically significant (P < 0.05), it was not clinically significant. It is unlikely that serum sCD23 would make a useful test for AIDS NHL because the magnitude of the difference between cases and controls was small and there was no change in serum sCD23 in cases that would indicate disease.

Aberrant expression of CD27 and soluble CD27 (sCD27) in HIV infection and in AIDS-associated lymphoma.

CD27 is a member of the tumor necrosis factor receptor superfamily that is expressed primarily on T cells, as well as on subsets of B cells and NK cells. CD70, which is expressed on activated B and T cells, but not on resting lymphocytes, is a ligand for CD27. Cell surface CD27 can be proteolytically cleaved to produce a 32-kDa soluble CD27 (sCD27) molecule. Elevated levels of sCD27 are seen in a number of disease states and malignancies. Although it has been reported that cerebrospinal fluid sCD27 levels were elevated in people who had AIDS dementia, little is known about CD27 expression in HIV disease. To determine if sCD27 levels were elevated in those with HIV infection, and/or in those with AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL), sCD27 levels were measured in HIV-negative and HIV-positive subjects as well as in people who developed AIDS-NHL. Serum sCD27 levels were seen to be elevated in HIV+ subjects. Furthermore, sCD27 levels were particularly elevated in those subjects who went on to develop AIDS-NHL, with serum sCD27 levels in AIDS-NHL subjects being significantly higher than those in HIV+ subjects who did not develop lymphoma. Most AIDS-NHL cell lines and primary AIDS-NHL tumor specimens expressed both CD27 and its ligand, CD70. The proportion of circulating B cells that expressed cell surface CD27 was substantially reduced in those with HIV infection, and B cells from HIV-infected subjects produced decreased levels of sCD27 in culture. Together, these results indicate that CD27/sCD27 expression is abnormal in HIV infection and suggest that this molecule merits further examination as a potential marker for AIDS-NHL.

Human herpesvirus 8-encoded interleukin 6 activates HIV-1 in the U1 monocytic cell line.

OBJECTIVE: Human herpesvirus 8 (HHV-8) encodes a viral interleukin 6 (vIL-6) which is structurally and functionally similar to human interleukin 6 (hIL-6). Since hIL-6 has been shown to upregulate the expression of HIV-1, the objectives of this study were to examine the ability of vIL-6 to upregulate HIV-1, and to determine the interactions of this virokine (viral cytokine) with the components of the interleukin 6 (IL-6) receptor complex. DESIGN AND METHODS: Recombinant HHV-8 vIL-6 (rvIL-6) was assayed for bioactivity in the IL-6-dependent cell line MH60.BSF2. HIV-1 p24 production by the U1 monocytic and ACH-2 T-cell lines, which are chronically infected with HIV-1, was used to assess the ability of vIL-6 to affect HIV-1 expression. hIL-6 and vIL-6 receptor utilization was determined by quantifying HIV-1 p24 production after neutralization of components of the IL-6 receptor complex, CD126'IL-6R' and CD130'gp130', on U1 cells with blocking antibodies. RESULTS: HHV-8 rvIL-6 was seen to have IL-6-like bioactivity in MH60.BSF2 cells, and readily upregulated HIV-1 p24 production in U1 monocytic cells, but not in ACH-2 T cells. The vIL-6 appeared to utilize the IL-6-specific component of the IL-6 signaling complex, CD126'IL-6R', in U1 cells. CONCLUSIONS: HHV-8 vIL-6 clearly has the potential to upregulate HIV-1 expression in monocytic cells, and therefore may play a role in AIDS pathogenesis in individuals infected with both viruses.

The development of AIDS-associated Burkitt's/small noncleaved cell lymphoma is preceded by elevated serum levels of interleukin 6.

B cell hyperactivation accompanies HIV infection and is believed to contribute to the increased incidence of B cell lymphoma in persons with AIDS. To examine B cell activation which precedes the development of AIDS-associated lymphoma, we measured levels of two B cell stimulatory molecules, soluble CD23 (sCD23) and interleukin 6 (IL6), in the serum of HIV-infected individuals prior to the diagnosis of lymphoma. Serum sCD23 was elevated in those subjects who developed lymphoma, compared to AIDS, HIV+, and HIV- controls (P = 0.001). Serum IL6 was significantly elevated in subjects who developed Burkitt's/small noncleaved cell lymphoma (BL/SNC, P = 0.01), but not in those subjects who developed large cell, immunoblastic, or central nervous system lymphomas, compared to CD4-matched AIDS controls who did not have lymphoma. These results suggest that lymphomagenesis of the BL/SNC subtype of AIDS lymphoma reflects B cell hyperactivation of a different nature from that which precedes other subtypes of AIDS-associated B cell lymphoma.

Increased immune activation precedes the inflection point of CD4 T cells and the increased serum virus load in human immunodeficiency virus infection.

The temporal relationship of serum levels of human immunodeficiency virus (HIV) RNA and of immune activation products in 10 HIV-seropositive persons who showed an accelerated decline (inflection point) in CD4 T cell counts and went on to develop AIDS and in 10 matched controls without inflection point were examined. Cases and controls did not differ statistically at the baseline time point for this study. CD4 cell inflection points occurred 18-30 months before AIDS development. Serum levels of soluble tumor necrosis factor receptor II, soluble interleukin-2 receptor, beta2-microglobulin, and neopterin increased significantly > or = 6 months before the CD4 cell inflection point. In contrast, increases in mean HIV RNA levels occurred at the time of the CD4 cell inflection point. These data are consistent with the view that in vivo immune activation precedes the increases in virus load and is followed by an accelerated and rapid loss of CD4 lymphocytes.

Immune dysfunction and the pathogenesis of AIDS-associated non-Hodgkin's lymphoma.

Much has been learned about how HIV-induced immune dysfunction contributes to B cell hyperactivation, and potentially, to the pathogenesis of AIDS-lymphoma. However, further studies are needed to fully understand how HIV infection and immune dysfunction promote B cell hyperactivation and the development/growth of AIDS-lymphoma. In particular, studies are needed to define the role of HHV8 vIL6, IL6 receptor-expression, and lymphocyte surface stimulatory molecules, in promoting B cell hyperactivation or lymphoma cell growth.

Monokine production following in vitro stimulation of the THP-1 human monocytic cell line with pertussis vaccine components.

Whole-cell pertussis found in diphtheria-tetanus-pertussis (DTP) vaccine can produce symptoms reminiscent of biological responses to circulating proinflammatory monokines such as IL-6, IL-1beta, and TNFalpha. Therefore the ability of pertussis-containing vaccines and several heat-killed Bordetella pertussis preparations to stimulate cytokine production in a human monocytic cell line, THP-1, were examined. The whole-cell pertussis vaccine induced significantly more IL-6, IL-1beta, and TNFalpha production than did the acellular pertussis or diphtheria-tetanus-only vaccine. Polymyxin B was able to inhibit most of the IL-6 induced by pertussis endotoxin and a heat-killed preparation of B. pertussis containing a null mutation in bvgAS, a regulatory locus required for expression of all known protein virulence factors synthesized by this organism. However, it only partially inhibited IL-6 production induced by other pertussis-containing preparations, including DTP vaccine. These results indicate that in vitro whole-cell vaccine is a potent stimulator of IL-6, IL-1beta, and TNFalpha. They also suggest that although endotoxin is a major inducer of IL-6, other components of B. pertussis also contribute to IL-6 production by monocytes.

IL-6 receptor (CD126'IL-6R') expression is increased on monocytes and B lymphocytes in HIV infection.

Interleukin-6 (IL-6) is a multifunctional cytokine, with a wide range of effects on various cell types, including several types of cells involved in immune responses. IL-6 is believed to be involved in the pathogenesis of several diseases and may contribute to AIDS pathogenesis in various ways. Elevated levels of IL-6 occur in HIV infection. The objective of this study was to define the distribution of the expression of the 80-kDa alpha subunit of the IL-6 receptor (CD126'IL-6R') on immune cell subpopulations in HIV-infected subjects. CD126 is responsible for IL-6 binding, and its expression determines which cells respond to this cytokine. An elevated number of monocytes, B cells, and CD4 T cells expressing CD126 were seen in the peripheral circulation of HIV-infected subjects when compared to HIV-seronegative control subjects. Also, an increase in the density of CD126 expression was noted on monocytes. Generally, the observed increases in CD126 did not correlate with CD4 levels in HIV-infected subjects or with disease status, with the exception of CD126 expression on CD8 T cells, which was lower in those HIV-infected subjects that had AIDS. In some cases, increased CD126 expressing cells showed higher levels of STAT3 phosphorylation on exposure to recombinant IL-6. These results indicate that greatly elevated levels of CD126-expressing cells, particularly B cells and monocytes, are seen in HIV infection and suggest that the altered expression of CD126 may contribute directly or indirectly to immune dysfunction and to AIDS pathogenesis in HIV infection.

Relationship of plasma HIV-RNA levels and levels of TNF-alpha and immune activation products in HIV infection.

The goal of this study was to determine the relationship between plasma human immunodeficiency virus (HIV) load and cytokine expression. HIV-RNA plasma levels were determined in 34 HIV-seropositive (HIV+) asymptomatic subjects [range: 0.5 to 211 kiloequivalents (kEq)/ml HIV-RNAJ, by a modified branched-DNA (bDNA) assay. Plasma HIV-RNA levels were positively correlated with increased plasma levels of TNF-alpha, soluble TNF receptor type II, soluble IL-2 receptor, beta 2-microglobulin, and neopterin, but not with plasma IL-6 levels. In contrast, increased viral load and diminished CD4 counts correlated weakly. TNF-alpha mRNA levels, as determined by bDNA technology, were not significantly increased in peripheral blood mononuclear cells (PBMC) isolated from HIV-infected subjects, compared to HIV-seronegative (HIV-) subjects, and were not correlated with plasma levels of HIV-RNA, cytokines, or activation markers. These results are consistent with the hypothesis that a self-reinforcing mechanism exists between TNF-alpha production and generalized immune activation on one hand with HIV replication on the other.

Interleukin 6 and AIDS-associated Kaposi's sarcoma: a nested case control study within the Multicenter AIDS Cohort Study.

Since the beginning of the AIDS epidemic, there has been considerable research on the etiology of Kaposi's sarcoma (KS) among HIV-infected individuals. A number of studies have confirmed that HIV or HIV-encoded products can interact with human cells to induce the production of cytokines, including interleukin 6 (IL-6). In vitro observations have indicated that AIDS-KS cells can produce significant levels of IL-6 and also respond to this cytokine. Preliminary data suggested that IL-6 may be elevated among HIV-infected individuals that subsequently develop AIDS-KS. The objective of this study was to determine if elevated levels of IL-6 are associated with an increased incidence of AIDS-KS compared to other AIDS-defining illnesses such as opportunistic infections (OIs). Serum IL-6 levels were determined by ELISA in frozen sera collected from participants in the Multicenter AIDS Cohort Study (MACS) at 6 months prior to AIDS diagnosis, in 73 cases (AIDS-KS), and 152 controls (OI). Elevated IL-6 levels were more prevalent among men with AIDS-OI than those with AIDS-KS: crude odds ratio (OR), 0.4 (95% CI, 0.2-0.9). Models of multivariate logistic regression were used to study potential confounders. Sexual behavior variables did not seem to confound the association between IL-6 and AIDS-KS. The higher prevalence of IL-6 among controls could be explained by the association of higher levels of IL-6 with lower levels of CD4 T cell number. IL-6 may be a marker of severe immune dysfunction among HIV-infected individuals.